The dichloromethane extract of the ethnomedicinal plant Neurolaena lobata inhibits NPM/ALK expression which is causal for anaplastic large cell lymphomagenesis

Unger,Christine; Popescu,Ruxandra; Giessrigl,Benedikt; Laimer,Daniela; Heider,Susanne; Seelinger,Mareike; Diaz,Rene; Wallnöfer,Bruno; Egger,Gerda; Hassler,Melanie; Knöfler,Martin; Saleh,Leila; Sahin,Emine; Grusch,Michael; Fritzer-Szekeres,Monika; Dolznig,Helmut; Frisch,Richard; Kenner,Lukas; Kopp,Brigitte; Krupitza,Georg

doi:10.3892/ijo.2012.1690

The dichloromethane extract of the ethnomedicinal plant Neurolaena lobata inhibits NPM/ALK expression which is causal for anaplastic large cell lymphomagenesis

Authors:
- Christine Unger
- Ruxandra Popescu
- Benedikt Giessrigl
- Daniela Laimer
- Susanne Heider
- Mareike Seelinger
- Rene Diaz
- Bruno Wallnöfer
- Gerda Egger
- Melanie Hassler
- Martin Knöfler
- Leila Saleh
- Emine Sahin
- Michael Grusch
- Monika Fritzer-Szekeres
- Helmut Dolznig
- Richard Frisch
- Lukas Kenner
- Brigitte Kopp
- Georg Krupitza
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Affiliations: Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria, Department of Pharmacognosy, University of Vienna, Vienna, Austria, Institute for Ethnobiology, Playa Diana, San José/Petén, Guatemala, Department of Botany, Museum of Natural History, A-1010 Vienna, Austria, Department of Obstetrics and Fetal-Maternal Medicine, Reproductive Biology Unit, Medical University of Vienna, Vienna, Austria, Department of Medicine I, Division: Institute of Cancer Research, Comprehensive Cancer Center, Medical University Vienna, A-1090 Vienna, Austria, Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, Vienna, Austria, Institute of Medical Genetics, Medical University of Vienna, A-1090 Vienna, Austria
Published online on: November 6, 2012 https://doi.org/10.3892/ijo.2012.1690
Pages: 338-348

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Abstract

The present study investigates extracts of Neuolaena lobata, an anti-protozoan ethnomedicinal plant of the Maya, regarding its anti-neoplastic properties. Firstly, extracts of increasing polarity were tested in HL-60 cells analyzing inhibition of cell proliferation and apoptosis induction. Secondly, the most active extract was further tested in anaplastic large cell lymphoma (ALCL) cell lines of human and mouse origin. The dichloromethane extract inhibited proliferation of HL-60, human and mouse ALCL cells with an IC50 of ~2.5, 3.7 and 2.4 µg/ml, respectively and arrested cells in the G2/M phase. The extract induced the checkpoint kinases Chk1 and Chk2 and perturbed the orchestrated expression of the Cdc25 family of cell cycle phosphatases which was paralleled by the activation of p53, p21 and downregulation of c-Myc. Importantly, the expression of NPM/ALK and its effector JunB were drastically decreased, which correlated with the activation of caspase 3. Subsequently also platelet derived growth factor receptor β was downregulated, which was recently shown to be transcriptionally controlled by JunB synergizing with ALK in ALCL development. We show that a traditional healing plant extract downregulates various oncogenes, induces tumor suppressors, inhibits cell proliferation and triggers apoptosis of malignant cells. The discovery of the ‘Active Principle(s)’ is warranted.

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